Thermocycling devices are apparatus for subjecting an object to a thermocycling protocol, i.e. to cycles in which the object is subjected to different temperatures in a repetitive fashion. Most commonly, these devices, also known as thermocyclers, are used in life science laboratories, where they are used for the amplification of nucleic acids according to a polymerase chain reaction (PCR) procedure. A thermocycler comprises a thermal block having facilities where samples can be placed. Furthermore, such device comprise a heating and cooling unit for raising and lowering the temperature of the block in discrete, pre-programmed steps. Basic principles of such thermocycling devices are for example disclosed in U.S. Pat. No. 5,038,852.
The device generates net heat which has to be dissipated. Otherwise, the overall performance of the device will suffer, i.e. the cooling and/or heating performance will decrease.
Excess heat generated in this process has thus to be discarded, or dissipated, into a heat sink from where it is, directly or indirectly, removed to the environment. This means, in turn, that the heat sink will become substantially warmer than the environment.
In the above identified environments, heat dissipation is a real challenge, especially when it comes to miniaturization of the devices, as it is required in high throughput laboratory environments, lab on a chip environments, highly integrated devices and the like.
For this reason, thermocyclers, especially peltier-equipped thermocyclers, comprise a large heat sink into which the generated heat is dissipated. These heat sinks are often connected to a cooling water circulation system being adjusted to a temperature of, e.g., 30° C. However, this results in additional apparatus requirements which are not compatible with the above identified miniaturization needs, and which mean high manufacturing costs and large maintenance efforts during operation.
Furthermore, it is desirable in many applications to speed up the thermocycling process. However, in a PCR protocol, for example, one can not simply shorten the duration of the different steps which take place at a given temperature (e.g. annealing, elongation and denaturation), as these are related to the efficiency of the process. The only option to speed up the process is to reduce the time the device needs to switch over from one step to the next, i.e. to heat up, or cool down, respectively, the sample holder with the samples comprised therein to the next temperature level. Thermocyclers comprising peltier elements suffer from this problem as well. Due to the limited heating and cooling performance of these devices, the time required for heating up or cooling down the sample holder is quite long in these thermocyclers, i.e. the so called “thermal ramps” are not very steep.
Considerable effort has been devoted to solve this problem. One approach is to reduce the thermal capacity of the sample holder, and to enhance the thermal conductivity of the sample holder as well as to enhance the thermal conductivity between the sample holder and the cooling and/or heating device. Another approach is to provide the sample holder with a thermally isolated lid. However, all these approaches do not fully satisfy the requirements related to speed of the thermocycling process.
WO 2006/105919 discloses a device for the simultaneous thermocycling of multiple samples comprising a thermal block, at least one heat pump, a heat sink, a control unit, and a thermal base which is in thermal contact with said heat sink and with said heat pump. The thermal base is a vapor chamber device especially a heat pipe for transporting and distributing heat. Using the thermal base in combination with the heat sink improves the heat dissipation and helps to decrease the required time for the cooling steps within the thermocycling protocol.
However, said thermal base does only enhance the heat dissipation by the heat sink. A disadvantage is that this effect is unidirectional, only affecting heat dissipation to the heat sink. Another disadvantage is that the thermal base can only be controlled in a way that the thermal base is switched “on” or “off”. Therefore, this thermal base is only a passively working dissipation device.